Tislelizumab, a PD-1 inhibitor for relapsed/refractory mature T/NK-cell neoplasms: Results from a phase 2 study.
Authors: Emmanuel Bachy, Kerry J. Savage, Huiqiang Huang, Yok-Lam Kwong, Giuseppe Gritti, Qingyuan Zhang, Anna Marina Liberati, Junning Cao, Haiyan Yang, Siguo Hao, Jianda Hu, Keshu Zhou, Filomena Russo, Huilai Zhang, Wei Sang, Jie Ji, Hui Liu, Sha Huang, Pier Luigi Zinzani
Journal: Journal of Clinical Oncology (2022)

7552 Background: Effective treatment choices for patients (pts) with relapsed/refractory (R/R) mature T/NK-cell neoplasms after failure of standard therapies are limited. Tislelizumab (TIS), a humanized anti-PD-1 mAb, demonstrated outstanding efficacy and favorable safety in pts with R/R classical Hodgkin lymphoma or solid tumors. We present safety and efficacy of the phase 2 study of TIS in pts with R/R mature T/NK-cell neoplasms. Methods: Pts were enrolled into 3 cohorts stratified by the type of T/NK-cell neoplasm to receive TIS 200 mg intravenously every 3 weeks until disease progression or intolerable toxicity. Eligible pts had ≥1 prior systemic therapy, disease progression during/after most recent therapy completion or refractory disease, ECOG ≤2, and life expectancy ≥6 mo. Primary endpoint was investigator-assessed overall response rate (ORR). Secondary endpoints included duration of response (DoR), complete response (CR) rate, progression-free survival (PFS), overall survival (OS) in cohorts 1 and 2, and safety. Results: 77 pts were treated. Cohort 1: R/R extranodal NK/T-cell lymphoma (n = 22); cohort 2: R/R mature T-cell neoplasms (n = 44; 21 peripheral T-cell lymphoma not otherwise specified; 11 angioimmunoblastic T-cell lymphoma; 12 anaplastic large cell lymphoma); cohort 3: R/R cutaneous T-cell lymphomas (CTCL; stage ≥1B; n = 11; 8 mycosis fungoides and 3 Sézary syndrome). Of all pts, 76.6% had advanced-stage disease, 51.9% had refractory disease, and 49.4% had ≥3 prior systemic regimens. Median treatment cycles for cohorts 1, 2, and 3 were 5 (range, 1-37), 4.5 (range, 1-38), and 17 (range, 3-25), respectively. Cohort 3 had promising efficacy (median follow-up [FU] 16.6 mo): ORR 45.5%; CR 9.1%; median DoR 11.3 mo (95% CI: 2.76-11.30); median PFS 16.8 mo; median OS not reached (NR). Modest efficacy was reported in cohort 1 (median FU 8.4 mo): ORR 31.8%; CR 18.2%; median DoR NR (95% CI: 2.66-not estimable [NE]); median PFS 2.7 mo; median OS 8.8 mo and also in cohort 2 (median FU 9.3 mo): ORR 20.5%; CR 9.1%; median DoR 8.2 mo (95% CI: 2.50-NE); median PFS 2.7 mo; median OS 13.3 mo. Most frequent adverse events (AEs) were pyrexia (32.5%), anemia (18.2%), arthralgia (18.2%), and diarrhea (15.6%); most frequent grade ≥3 AEs were anemia (7.8%), pneumonia (6.5%), and neutropenia (5.2%). Any grade immune-mediated AEs occurred in 22 (28.6%) pts, most frequently hypothyroidism (10.4%), hyperglycemia (5.2%), and rash (5.2%); and grade ≥3 in 4 (5.2%) pts (blood creatine phosphokinase increased, hepatitis, hypothyroidism, rash, and urticaria [1 pt each]). No treatment-related AEs led to death. Conclusions: TIS was well tolerated, achieving modest efficacy in R/R mature T/NK-cell neoplasms, with some long-lasting remissions particularly in CTCL. Further studies are warranted to determine the biologic features associated with response and explore optimal combination therapies. Clinical trial information: NCT03493451.